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基因组学时代天然产物在药物发现中的再兴起。

The re-emergence of natural products for drug discovery in the genomics era.

机构信息

1] Research and Innovation Support, Dublin City University, Dublin 9, Ireland. [2] Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0NR, UK.

Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow G4 0NR, UK.

出版信息

Nat Rev Drug Discov. 2015 Feb;14(2):111-29. doi: 10.1038/nrd4510. Epub 2015 Jan 23.

Abstract

Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

摘要

天然产物一直是药物发现的化合物的丰富来源。然而,在过去的二十年中,它们的使用有所减少,部分原因是由于针对分子靶点的高通量测定筛选天然产物存在技术障碍。在这里,我们回顾了利用最近的技术进步来减少这些障碍的天然产物筛选策略。我们还评估了基因组和代谢组学方法在增强天然产物传统研究方法中的应用,并强调了天然产物在抗菌药物发现和作为蛋白质-蛋白质相互作用抑制剂方面的最新实例。对功能测定和表型筛选的认识不断提高,可能会进一步促进人们对天然产物在药物发现中的兴趣的复苏。

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